AnnexinA7 down-regulation might suppress the proliferation and metastasis of human hepatocellular carcinoma cells via MAPK/ ERK pathway.

BACKGROUND

Hepatocellular carcinoma is one of the most fatal malignancies worldwide with high lethality. However, the exact mechanism of liver tumorigenesis is still unclear. AnnexinA7 (ANXA7) is a Ca2+-binding protein which is involved in membrane organization and dynamics and indicated a role of ANXA7 in cancer. However, the action of ANXA7 in hepatocellular carcinoma and the relative mechanism is still indistinct.

OBJECTIVE

To gain more insight into the biological function of ANXA7 and assess its possible influence on proliferation and metastasis capacity of human hepatocellular carcinoma cells with the relative mechanism.

METHODS

ANXA7 was down-regulated by RNA interference in both HepG2 and smmc-7721 cells. The decreased cell proliferation was detected by MTT method and colony formation assay. To confirm the result of cell proliferation, Ki-67 and cyclinD1 expression was examined by Western Blot. The increased apoptosis capacity of the cells was detected with cell cytometry and PI staining respectively. Bcl-2 and Bax expression was further investigated by Western blot and the decreased ration of Bcl-2/Bax might explain the increased apoptosis.

RESULTS

Cell metastasis showed significantly limited ability which was tested by wound healing assay and Transwell assay. Meanwhile, the key biomarkers of cell metastasis E-cadherin expression increased while MMP-9 decreased. Furthermore, we found that ANXA7 played its role via MAPK/ERK pathway.

CONCLUSIONS

ANXA7 might involve in the development of hepatocellular carcinoma and act as an oncogene which might be a potential therapeutic target for treatment.